Introduction
Leptin is a peripheral signal chiefly responsible for the regulation of energy homeostasis via actions at the arcuate nucleus. The accompanying hypertension and high sympathetic activity has been suggested to be due to downstream activation of alpha- Melanocortin Stimulating Hormone (α-MSH) containing pathways. We therefore aimed to investigate the cardiovascular and RSNA response to α-MSH in obesity related hypertension.
Methodology
Male New Zealand White rabbits were instrumented with an intracerebroventricular cannula (ICV), renal sympathetic nerve electrode and ear artery cannula for MAP measurement. Animals were fed a high fat diet (HFD;13.5% fat,n=11) or a normal fat diet (NFD; 3.5 % fat, n=11) for 3 weeks in order to develop obesity related hypertension; then cardiovascular and RSNA responses to icv injections of α-MSH were assessed in conscious rabbits.
Results
At 3 weeks HFD rabbits had higher MAP, HR, RSNA and plasma leptin levels (P<0.05 for all) compared with controls. ICV α-MSH (3-10 nmol) increased RSNA and HR (P<0.01) in HFD but not NFD rabbits. By contrast α-MSH produced 70% less c-Fos expression in the dorsomedial, paraventricular and ventromedial hypothalamus of HFD rabbit compared with controls. Activation of the arcuate nucleus was similar in both groups. This pattern closely follows previous findings with ICV leptin.
Conclusion
These findings suggest that HFD induced facilitation of central autonomic pathways involving leptin and α-MSH may explain the obesity related hypertension by increasing renal sympathetic nerve activity.